The long-term objective of this research proposal is to understand the role of inflammatory mechanisms on endothelial dysfunction, an early and potentially reversible stage of atherosclerosis, in women with systemic lupus erythematosus (SLE). Dr. Rhew is in her second year of a faculty appointment in the Division of Rheumatology at Northwestern University. She is seeking a mentored career development award in order to achieve her goal of developing into an independent clinical research investigator. She has recently completed the Masters of Science in Clinical Investigation program, and will be taking additional courses in the Masters in Public Health program during the award period. She has the support of her primary mentor, Dr. Ramsey-Goldman who is an NIH funded, internationally recognized expert in SLE epidemiology with extensive mentoring experience, as well as Drs. McPherson, Pearce, and Dyer, her secondary mentors, who have expertise in cardiovascular imaging, vascular biology, and cardiovascular epidemiology/biostatistics. The proposed project capitalizes on the infrastructure of an ongoing NIH-sponsored, longitudinal, epidemiologic study being conducted by the applicant's primary mentor. It is known that the risk of premature cardiovascular disease (CVD) is elevated in SLE women and is not completely explained by traditional risk factors. The central hypothesis underlying this current proposal is that inflammation, as reflected by: inflammatory markers (IL-6, CRP, plasminogen activator inhibitor-1); SLE disease activity or chronic disease damage; and visceral adiposity/insulin resistance is related to endothelial dysfunction, an early and reversible physiological marker of sub clinical CVD, in SLE women. Endothelial function will be measured non-invasively using brachial reactivity ultrasound. Relevance to Public Health: At the completion of this project, we expect to have characterized important risk factors related to inflammation that may account for the additional CVD risk that is not fully explained by traditional risk factors in SLE women. In addition, we plan to utilize a non-invasive test (Brachial Reactivity Ultrasound) to identify patients at an early and potentially reversible stage of CVD. In doing so, our findings will provide further insights into pathogenic mechanisms underlying the increased risk of CVD in SLE women, and identify potential targets for intervention and prevention (e.g. treatments targeted at specific inflammatory mediators; treatments targeted at the inflammation related to SLE disease; exercise and dietary measures to reduce visceral fat and increase insulin sensitivity; and treaments targeted at improving insulin resistance) in order to reduce the morbidity and mortality associated with CVD in SLE women. [unreadable] [unreadable] [unreadable] [unreadable]